Biomarkers may help predict outcomes in gastric cancer patients who abuse alcohol

January 10, 2018, Elsevier
Immunohistochemical staining of transcription factor IIB-related factor 1 (BRF1) in gastric cancer (GC). A and B: High BRF1 expression in GC tissue. C: Positive BRF1 expression in GC para-tumor tissue. D and E: Low BRF1 expression in GC tissue. F: Negative BRF1 expression in GC para-tumor tissue. Original magnification: x100 (A and D); x400 (B, C, E, and F). Credit: The American Journal of Pathology

Alcohol consumption has been identified as a modifiable risk factor for cancers such as gastric cancer. A new report in the The American Journal of Pathology sheds light on how specific proteins interact with alcohol, and how that interplay impacts survival and response to platinum-based adjuvant chemotherapy in patients with gastric cancer who may or may not still be drinking. It is the first time that a correlation between a key microRNA-processing modulator, transcription factor IIB-related factor 1 (BRF1), and prognosis of gastric cancer patients has been demonstrated. Investigators also determined that breast cancer susceptibility gene BRCA1/2, and myeloperoxidase (MPO) are more frequent in gastric cancer patients who engage in hazardous or harmful alcohol consumption.

"Alcohol consumption is a known risk factor for gastric cancer, which carries high morbidity and mortality in China. We found that DNA repair-related markers—BRF1, BRCA1/2, and MPO—have good prognostic value in gastric cancer with or without harmful consumption habits. Moreover, these proteins are also associated with how effective platinum-based adjuvant chemotherapy will be for gastric cancer patients," explained Hua Wang, MD, PhD, and co-senior author Kangsheng Gu, MD, PhD, both of the Department of Oncology at First Affiliated Hospital of Anhui Medical University, Hefei, Anhui (China).

Researchers analyzed tumor tissue from 77 patients who had undergone surgery for primary gastric adenocarcinoma and 69 tissue samples taken from outside the tumor area. Among them, 66 patients received radical surgery and 57 patients received platinum-based adjuvant chemotherapy. All 77 patients were followed for an average of 18 months, during which time 94% (62/66) experienced disease recurrence. Patients remained free of disease for an average of 14 months (disease free survival, DFS) whereas the median overall survival (OS) was 20 months.

BRF1, BRCA1/2, and MPO were also helpful in predicting which patients would benefit more from platinum-based adjuvant chemotherapy. For example, DFS was extended two-fold or more in patients who underwent chemotherapy and showed negative or low BRCA1/2 expression. For those with negative or low BRCA1, the average disease-free interval was 18 months compared to nine months in the high-expression group. Patients with negative MPO also had a better outcome trend, although it was not statistically significant.

Importantly, investigators found that alcohol continued to have a detrimental effect in patients. High BRF1 expression and MPO-positive inflammatory cell infiltration were more frequent in gastric cancer patients with hazardous or harmful alcohol consumption habits. Abnormal changes in BRCA1 in tissues outside the tumors were more frequent in alcohol abusers. In previous studies, these investigators found similar correlations between BRF1 and alcohol consumption in breast and liver patients.

Understanding the mechanisms of how these proteins interact with alcohol and contribute to carcinogenesis is still being investigated. It is thought that RNA Pol III transcribes genes play a crucial role in alcohol-mediated tumorigenesis. BRF1 regulates RNA Pol III gene transcription, and its overexpression acts though BRCA1 to alleviate inhibition of RNA Pol III transcription. Measurement of MPO is interpreted as a measure of the gastric inflammation and oxidative damage induced by alcohol. BRCA1/2 and MPO also play key roles in DNA damage repair.

"Until now, there have been no good markers to indicate in tissue," noted Dr. Wang. "Future larger clinical trials are planned to explore the prognostic utility of these biomarkers in gastric and other cancers in patients who consume hazardous quantities of alcohol."

Explore further: Increase in risk of certain gastric cancer from heavy drinking

More information: Yiyin Zhang et al, Prognostic Value of the Expression of DNA Repair–Related Biomarkers Mediated by Alcohol in Gastric Cancer Patients, The American Journal of Pathology (2018). DOI: 10.1016/j.ajpath.2017.10.010

Related Stories

Increase in risk of certain gastric cancer from heavy drinking

May 18, 2011
The results from a very well-done meta-analysis support other data generated on the risk of alcohol consumption and gastric cancer – that is – that the risk may be real for heavy alcohol consumption but not for ...

Early drivers of gastric cancer

August 9, 2017
Gastric cancer – a leading cause of cancer-related deaths worldwide – is commonly diagnosed at a late stage when most patients have a poor prognosis.

Mutational signatures may ID pts with Br Ca most likely to benefit from platinum-based chemo

December 19, 2017
The presence in advanced breast cancer of mutational signatures characteristic of homologous recombination deficiency (HRD) was associated with improved clinical outcomes to treatment with platinum-based chemotherapy.

Treatment based On BRCA1 level does not increase survival of stage II/III NSCLC N+ resected patients

October 17, 2017
New research shows that treating stage II and III non-small cell lung cancer (NSCLC) N+ resected patients with customized chemotherapy (CT) treatment based on their specific BRCA1 expression levels, as opposed to providing ...

Even one drink a day can increase risk of cancer, study finds

November 13, 2017
Do you enjoy the occasional cocktail? Beware, because even moderate consumption of alcohol can increase your risk of cancer, according to a new report.

Differences in subtypes of gastric cancer may determine prognosis and response to treatment

July 26, 2017
Molecular classification of the four distinct subtypes of gastric cancer could potentially shape tailored treatment options by helping to predict survival outcomes and patients' response to chemotherapy.

Recommended for you

The pill lowers ovarian cancer risk, even for smokers

January 18, 2018
(HealthDay)—It's known that use of the birth control pill is tied to lower odds for ovarian cancer, but new research shows the benefit extends to smokers or women who are obese.

Single blood test screens for eight cancer types

January 18, 2018
Johns Hopkins Kimmel Cancer Center researchers developed a single blood test that screens for eight common cancer types and helps identify the location of the cancer.

Researchers find a way to 'starve' cancer

January 18, 2018
Researchers at Vanderbilt University Medical Center (VUMC) have demonstrated for the first time that it is possible to starve a tumor and stop its growth with a newly discovered small compound that blocks uptake of the vital ...

How cancer metastasis happens: Researchers reveal a key mechanism

January 18, 2018
Cancer metastasis, the migration of cells from a primary tumor to form distant tumors in the body, can be triggered by a chronic leakage of DNA within tumor cells, according to a team led by Weill Cornell Medicine and Memorial ...

Modular gene enhancer promotes leukemia and regulates effectiveness of chemotherapy

January 18, 2018
Every day, billions of new blood cells are generated in the bone marrow. The gene Myc is known to play an important role in this process, and is also known to play a role in cancer. Scientists from the German Cancer Research ...

These foods may up your odds for colon cancer

January 18, 2018
(HealthDay)—Chowing down on red meat, white bread and sugar-laden drinks might increase your long-term risk of colon cancer, a new study suggests.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.